The program is an integrated, multidisciplinary Phase II and III cancer control project. It focuses on the possibilities suggested by epidemiological, clinical and experimental studies for pharmacologic intervention, chemoprevention, in women at increased risk for breast cancer. The individual projects are based on an endocrine biomarker (Project 1) which requires validation in a Phase II study. Phase II pilot interventions, using an endocrine (L-thyroxine: Project 2) and nutritional approach (omega-3 fatty acids: Project 3) implemented to gain knowledge which can be applied to a Phase III randomized trial. In order to define the study population both genetic (Project 5) and histopathologic (clinical core) criteria will be used. To enable us to reach the target population effectively and maximize consent and adherence psychosocial studies are proposed (Project 4). The Phase II projects culminate in a Phase III randomized, double-blind, controlled clinical trial aimed at studying the ability of one, or both, these interventions to favorable perturb a biomarker. This approach represents a short-term (project period) goal which may lead to our ultimate long-term objective of the reduction of human breast cancer rates.